Immunotherapy of AL amyloidosis

Alan Solomon, Deborah T. Weiss, Jonathan Wall

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

I. INTRODUCTION Presently, therapeutic options for patients with primary systemic (AL) amyloidosis are limited to reducing light chain synthesis using anti-plasma cell chemotherapy given in conventional amounts or high doses combined This approach, particularly dose-intensive therapy, has extended However, such treatment can be associated with numerous complications 4 and an exceedingly high mortality rate, especially in the elderly or Importantly, amyloid deposition is not necessarily irreversible, as evidenced experimentally 6 and clinically in Compelling evidence of in situ resolution of AL deposits has come from chemical analyses of fibrillar extracts where it has been determined that, most often, the protein constituents are not composed of intact light chains, but rather, consist of fragments that seemingly result from proteolytic degradation. 9 The failure of the body to remove such material totally may be attributed to its non-foreign nature or the presence of other co-depositing components, e.g., glycosaminoglycans or P-component that have been alleged to interfere with amyloidolysis.10,11 II. AMYLOID-REACTIVE ANTIBODIES To investigate humoral or cellular factors that could facilitate AL resolution, we developed an in vivo animal model in which amyloidomas were produced in mice by subcutaneous injection between the scapula of up to 200 mg of water-soluble human AL extracts. We found that this substance was removed by an immune mechanism associated with the generation of amyloid-reactive antibodies that recognized, as evidenced using in vitro assays, the light chain constituent of the amyloid protein injected, as well as heterologous ALN or ALO Additionally, when the fibrillar preparation was re-administered to immunized animals, the rate of disappearance increased approximately two-fold. Elimination of amyloid tumors also was expedited when the extracts were first incubated overnight with mouse immune serum. Further, the resolving amyloidomas were extensively infiltrated by activated neutrophils. Under similar conditions, amyloidolysis was not accelerated in immunodeficient (SCID) mice or in animals where the neutrophils were suppressed by administration of an anti-neutrophil mAb or were functionally impaired, i.e., in CD-18 knockout mice.

Original languageEnglish (US)
Title of host publicationAmyloid and Amyloidosis
PublisherCRC Press
Pages479-481
Number of pages3
ISBN (Electronic)9781420037494
ISBN (Print)0849335345, 9780849335341
StatePublished - Jan 1 2004

Fingerprint

Amyloidosis
Amyloid
Immunotherapy
Neutrophils
Light
Amyloidogenic Proteins
Scapula
SCID Mice
Antibodies
Subcutaneous Injections
Plasma Cells
Glycosaminoglycans
Knockout Mice
Immune Sera
Therapeutics
Animal Models
Drug Therapy
Mortality
Water
Neoplasms

All Science Journal Classification (ASJC) codes

  • Medicine(all)
  • Immunology and Microbiology(all)
  • Neuroscience(all)

Cite this

Solomon, A., Weiss, D. T., & Wall, J. (2004). Immunotherapy of AL amyloidosis. In Amyloid and Amyloidosis (pp. 479-481). CRC Press.

Immunotherapy of AL amyloidosis. / Solomon, Alan; Weiss, Deborah T.; Wall, Jonathan.

Amyloid and Amyloidosis. CRC Press, 2004. p. 479-481.

Research output: Chapter in Book/Report/Conference proceedingChapter

Solomon, A, Weiss, DT & Wall, J 2004, Immunotherapy of AL amyloidosis. in Amyloid and Amyloidosis. CRC Press, pp. 479-481.
Solomon A, Weiss DT, Wall J. Immunotherapy of AL amyloidosis. In Amyloid and Amyloidosis. CRC Press. 2004. p. 479-481
Solomon, Alan ; Weiss, Deborah T. ; Wall, Jonathan. / Immunotherapy of AL amyloidosis. Amyloid and Amyloidosis. CRC Press, 2004. pp. 479-481
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